Digital Commons Network^™

Multiscale Modeling Of Cardiac Growth And Baroreflex Control, Hossein Sharifi

Theses and Dissertations--Mechanical and Aerospace Engineering

The heart functions within a complex system that adapts its function to any alteration in loading via several mechanisms. For example, the baroreflex is a short-term feedback loop that modulates the heart's function on a beat-to-beat basis to control arterial pressure. On the other hand, cardiac growth is a long-term adaptive response that occurs over weeks or months in response to changes in left ventricular loading. Understanding the mechanisms that drive ventricular growth and biological remodeling is critical to improving patient care. Multiscale models of the cardiovascular system have emerged as effective tools for investigating G&R, offering the ability to …

Assessment Of The Interplay Between Regional Β-Amyloid Burden And White Matter Hyperintensities On Cognition And Default Mode Network In Clinically Normal Older Participants, Doaa G. Ali

Theses and Dissertations--Clinical and Translational Science

Objective: Alzheimer’s disease (AD) and subcortical vascular dementia are considered the most common pathologic contributors to dementia in the aging population. Both frequently coexist in over 80% of community dwelling adults with dementia. The neuropathological development of AD arguably begins with β-amyloid (Aβ) deposition in the brain. This series of studies aims to test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in preclinical AD (pAD) (study1). Since mixed dementia is widely recognized as the norm rather than the exception, the second study aimed to explore the …

Enhancing Dna-Damaging Therapy Through The Inhibition Of Dntp Synthesis Using A Synergistic Drug Combination To Treat Pancreatic Neuroendocrine Neoplasms, Jennifer Castle Md

Theses and Dissertations--Clinical and Translational Science

Despite clinical advances, pancreatic neuroendocrine neoplasms (pNEN) remain a difficult clinical entity to treat and can carry a poor prognosis. Systemic therapy is used to treat pNENs which are not amenable to surgical resection. Peptide receptor radionuclide therapy, a form of radiation therapy (RT) and cisplatin are two different forms of DNA-damaging therapy in current use to treat pNENs. However, their efficacy remains poor as single agents. This study aimed to increase the sensitivity of pNENs to the DNA-damaging agents, RT and cisplatin, by inhibiting deoxynucleotide triphosphate (dNTP) synthesis. Triapine, a ribonucleotide reductase inhibitor (RNRi), and ataxia telangiectasia and Rad3-related …

Role Of Autophagy In Aortic Aneurysms, Aida Javidan

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal Aortic Aneurysms (AAAs) are permanent dilations of the abdominal aorta with greater than 80% mortality after rupture. Currently, there are no proven non-surgical therapeutics to blunt expansion or rupture, which highlights the need to gain mechanistic insights into AAA formation. AAA formation involves a complex process of destruction of aortic media through activation of matrix metalloproteinases (MMPs), loss of smooth muscle cells, degradation of extracellular matrix proteins like elastin and collagen, and inflammation. Autophagy is a well-conserved cellular process whereby damaged cytoplasmic organelles and long-lived proteins are degraded. Cellular autophagic activity is usually low under normal conditions but can …

The Role Of High Mobility Group Box-1 Pathobiology In Angiotensin Ii-Induced Abdominal Aortic Aneurysms, Shayan Mohammadmoradi

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysms (AAAs) are permanent luminal dilations of the vessel wall that can result in rupture and death. There is currently no evidence-based treatment to prevent or attenuate the development of this devastating condition. Although vascular inflammation is known to be one of the hallmarks of AAA, underlying mechanisms that initiate inflammatory pathways in the aorta are not clearly known. High-mobility group box 1 (HMGB1), a highly conserved nonhistone DNA-binding nuclear protein, may contribute to vascular diseases. Since whole-body genetic deletion of HMGB1 is embryonic lethal, pharmacological approaches have been used to manipulate HMGB1 in mice. However, it remains …

Age- And Sex-Dependent Alterations In Primary Somatosensory Neuronal Calcium Network Dynamics During Locomotion, Sami L. Case

Theses and Dissertations--Pharmacology and Nutritional Sciences

Over the past 30 years, the calcium (Ca2+) hypothesis of brain aging has provided clear evidence that hippocampal neuronal Ca2+ dysregulation is a key biomarker of aging. Indeed, age-dependent Ca2+-mediated changes in intrinsic excitability, synaptic plasticity, and activity have helped identify some of the mechanisms engaged in memory and cognitive decline. However, much of this work has been done at the single-cell level, mostly in slice preparations, and in restricted structures of the brain. Recently, our lab identified age- and Ca2+-related neuronal network dysregulation in the cortex of the anesthetized animal. Still, investigations in the awake animal are needed to …

Relative Adrenal Insufficiency In Sepsis, Dan Hao

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death in children. Glucocorticoid (GC) therapy had been strongly recommended for the pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. Relative adrenal insufficiency (RAI) is a condition characterized by impaired inducible glucocorticoid (iGC) production in response to stress. It develops in 32.8% of pediatric septic patients. Unfortunately, little is known about the pathogenesis of RAI in pediatric sepsis, and whether GC therapy should be based on the status of RAI is controversial. In this study, we utilized 21-day-old SF1CreSRBI^fl/fl mice as the first …

Age-Associated Increase Of Gamma Delta T Cells In Visceral Adipose Tissue And Mechanisms Of Their Accumulation, Sujata Mukherjee

Theses and Dissertations--Pharmacology and Nutritional Sciences

Chronic systemic inflammation, known as inflammaging is considered a hallmark of aging and associated diseases. While adipose tissue has long been considered only as a caloric reservoir regulating systemic energy homeostasis, research in the past couple of decades substantiate its endocrine function to secrete an array of inflammatory mediators and hormones, which have physiological effects on multiple organ systems, and contribute to inflammaging. Redistribution of adipose tissue from subcutaneous to visceral depots, changes in the immune profile and the chronic inflammatory state are among the major sources of adipose tissue dysfunction with aging.

This dissertation is focused on identifying and …

Exploring The Efficacy Of Mir-33 Antagonism In Promoting Regression Of Intracranial Atherosclerosis In A Nonhuman Primate Model, Peter Hecker

Theses and Dissertations--Pharmacology and Nutritional Sciences

Atherosclerosis, characterized by lipid accumulation and arterial inflammation, is a major contributor to global morbidity and mortality. Despite significant progress in understanding atherosclerosis in extracranial arteries, the study of intracranial atherosclerosis (ICAS) has been relatively neglected, despite its crucial role in stroke and vascular cognitive impairment. Challenges related to ICAS, including its location within the cranium and limited availability of suitable animal models, have hindered research progress in this area. Although nonhuman primates (NHPs) are commonly used for studying extracranial atherosclerosis, a comprehensive understanding of ICAS pathophysiology in these animals is lacking. By subjecting NHPs to a high-fat/cholesterol diet, we …

The Role Of Renal-Derived Human Soluble Prorenin Receptor In Blood Pressure Regulation And Kidney Function, Gertrude Arthur

Theses and Dissertations--Pharmacology and Nutritional Sciences

The soluble prorenin receptor (sPRR) is a cleaved form of the full-length prorenin receptor (PRR). It has been demonstrated to activate the renin-angiotensin system (RAS) independent of its full-length receptor and mediate similar physiological and pathophysiological processes, albeit via different mechanisms.

The sPRR hormone, a component of RAS, has been identified as a plasma biomarker for hypertension and cardiovascular diseases in humans. In mice, sPRR infusion has been shown to mediate blood pressure elevation through competitive AT1R binding and activation. However, the biological contribution of renal-derived human sPRR to blood pressure regulation and kidney function remains unknown. Therefore, this study …

Sex Dimorphisms Of Aldosterone And High Salt Induced Aortic Aneurysms In Mice, Xufang Mu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Aortic aneurysms, a permanent enlargement in the aorta, is a devastating disease with a high mortality rate after rupture. Aortic aneurysms exhibit strong sex dimorphisms: men are at higher risk than women while women experience worse outcomes if diagnosed. Currently, the only intervention is by open surgery or endovascular repair, and no drugs are approved for blunting the disease progression. This highlights the needs for mechanistic studies for sex-specific therapeutic targets.

Our lab established the mouse model in which mineralocorticoid receptor (MR) agonist aldosterone induces aortic aneurysms in the presence of high salt in male mice age-dependently, mimicking the aging …

The Influence Of Apoe Genotype On Lipid Droplet Dynamics, Cassi Friday

Theses and Dissertations--Physiology

Excess lipid droplet (LD) accumulation is associated with several pathological states, including neurodegenerative disorders such as Alzheimer’s disease (AD). However, the mechanism(s) by which changes in LD composition and dynamics may contribute to the pathophysiology of AD remains unclear. Apolipoprotein E (ApoE) is a droplet-related protein with a common variant (ApoE4) that confers the largest increase in genetic risk for late-onset AD. Interestingly, ApoE4 is associated with both increased neuroinflammation and excess LD accumulation. This dissertation work seeks to quantitatively profile the lipid and protein composition of LDs between the ‘neutral’ ApoE3 and ‘risk’ ApoE4 isoforms, in order to gain …

Clinical And Biological Factors Determine Spinal Cord Injury Outcomes: Liquor To Lipids, Ethan Glaser

Theses and Dissertations--Physiology

Spinal cord injuries (SCI) are debilitating and life altering events that can lead to permanent motor and sensory loss. SCI outcomes are impacted by both clinical factors such as blood alcohol content (BAC) at the time of injury as well as biological factors like the lipid-rich myelin debris that accumulates in the injury site. Both clinical and biological factors contribute to SCI recovery, impacting neuroinflammation, locomotor recovery, and histopathology. The purpose of the studies described here is to investigate the role of acute alcohol intoxication and intracellular lipid processing pathways on SCI outcomes in a rodent model.

An elevated BAC …

Dosimetric And Clinical Investigation Into Dose Variations Of The Target And Organs At Risk In High Dose Rate Gynecological Brachytherapy, Brien Washington

Theses and Dissertations--Radiation Medicine

The technological advancements in brachytherapy have allowed for increased precision and better-quality treatments. This is apparent in treating GYN cancers of the uterine cervix. Lengthy low dose rate (LDR) treatments, implant systems, and two-dimensional (2D) image-guided treatments have been replaced by quicker high dose rate (HDR) treatments and adaptive treatment planning with three-dimensional (3D) imaging modalities. However, this increased precision can result in reduced dosimetric accuracy. Implant systems were designed to conform to the prescribed dose, and 2D plans were only concerned with dose to two organs at risk (OAR) parameters. Now, planners must consider added OAR position data and …

Understanding The Effects Of Age, Environmental Conditions, And Placement On Cockroach Gel Bait Performance, Isabelle Lucero

Theses and Dissertations--Entomology

Cockroach baits are one of the most effective tools used for German cockroach (Blattella germanica L.) control. This is due in part to the number of cockroach baits on the market with various matrix compositions and active ingredients, aiding in the control of resistant (physiologically and behaviorally) cockroach populations through bait rotation. However, it remains unclear how cockroach gel baits perform over time and under different environmental conditions. Therefore, we aged six cockroach gel baits for varying times (24 hours, one month, three months, six months) and at three relative humidities (15%, 40%, and 80%), and tested their performance …

Assessing 4-H And Its Circle Of Courage In A Psychiatric Residential Treatment Facility: A Case Study, Elizabeth Steering

Theses and Dissertations--Family Sciences

This 4-H case study takes place in a psychiatric residential treatment facility (PRTF) in Kentucky. The PRTF provides clinical services to youth that are not able to be safely maintained in their homes due to having demonstrated unsafe or harmful behaviors. Youth admitted to the PRTF stay for an average of three to six months while they receive intensive therapeutic and psychiatric care as well as medical treatment and public schooling. The current case study incorporates programming from 4-H, which is the youth development program of the Cooperative Extension System (CES) and the National Institute of Food and Agriculture (NIFA), …

Conceptualizing Asexual Identities, Miranda L. Bejda

Theses and Dissertations--Family Sciences

In current literature, there is little congruence on an inclusive definition of human asexuality. This study explored individuals’ self-identification with asexuality as well as their conceptualization of that identity via thematic analysis. Using a Qualtrics XM survey, 374 individuals (18+ years old) answer questions regarding their experience as a person identifying themselves as asexual. Identity label authenticity, perceived impact of compulsory heterosexuality and heteronormativity on participants' current identity within the asexual spectrum, and prescribed heteronormative ideals were correlated. Thematic analysis revealed themes such as confusion about identity membership, feeling abnormal, the burden of living in a heteronormative society, and identity …

Mechanisms Of Rnai In Insects, Jin Mo Koo

Theses and Dissertations--Entomology

RNA interference (RNAi) mechanism is found in many eukaryotes and animal cells, with its endogenous functions as defense against transposable elements and viruses, as well as post transcriptional regulation of gene expression. Since its first discovery, RNAi has contributed enormously as a reverse genetic tool for functional genomic studies. In application, RNAi is used in therapeutics, as well as agricultural crop and livestock protection. Yet, for the wider application of RNAi, improvement of its potency and delivery technologies is needed. Deeper mechanistic understanding of every step of RNAi, from cellular uptake of RNAi trigger molecule to targeted mRNA degradation is …

Costs And Benefits Of Integrating Poultry Into Cover Crop - Vegetable Rotations, Viktor Halmos

Theses and Dissertations--Entomology

Integrated livestock systems were once common leading up to the 20th century where livestock generated manure that was then used to fertilizer crop production in a closed- or semi-closed system. However, with the industrialization of agriculture in the mid to late 20th century, specialization drove simplified systems that segregated livestock from cropping systems. This segregation led to nutrient surpluses occurring in livestock operations, and nutrient demands in cropping systems creating a plethora of environmental issues. With the increased awareness of environmental issues, a renewed interest in integration has driven producers and researchers to experiment with integration again. For research, the …

Exploring The Effects Of Environmental Factors On Rice Blast Disease, April Ellen Lamb

Theses and Dissertations--Plant Pathology

Rice blast disease, caused by the ascomycete fungus Magnaporthe oryzae, occurs in over 85 countries and results in an annual crop loss of 10-30%, a corresponding nutrient value of meals for 60 million people. As a result, it is listed as a critical plant disease by the United Nations. Understanding factors affecting disease severity is of critical concern for food security. M. oryzae has been used as a model system for studying effector-triggered immunity (ETI) by understanding that ETI is primarily a plant response. M. oryzae has been used as a model to study fungal pathogenicity, host specificity, genome …

Molecular Genetic Studies Of Horses, Especially With Reference To Aggrecan And Dwarfism, John Edmund Eberth

Theses and Dissertations--Veterinary Science

This work consists of studies on dwarfism in Miniature horses and a study on breakdowns in Thoroughbreds in relation to gene aggrecan. A correction of the description and designation of D3 dwarf variant in aggrecan (ACAN) from the master’s thesis Chondrodysplasia-like dwarfism in the Miniature horse (2013). Commercial sequencing showed previous sequencing reads presented an artifact and not a single base deletion. Analysis showed a single base missense mutation in exon 8 identified as D3* was the actual cause. Multiple alleles of ACAN associated with chondrodysplastic dwarfism in Miniature horses by Eberth et al. (2018), corrected the …

Computed Tomography Image Analysis: Modeling Skeletal Injuries In Thoroughbred Racehorses, Grace Louise Camp

Theses and Dissertations--Veterinary Science

Musculoskeletal injuries account for the majority of career-ending health concerns in Thoroughbred racehorses. A small but very serious subset of these can be life-threatening and usually involve fractures of the bones in the lower limb that occur during high-speed exercise or racing competitions. Understanding the etiopathogenesis of lower forelimb bone fractures leading to catastrophic musculoskeletal injuries (CMI) is the highest safety and welfare priority in horse racing. This thesis conducted two studies utilizing computed tomography (CT) images of Thoroughbred lower limbs. The first examined bone lesion annotations in 134 horses (268 forelimbs) across 105 anatomical sites to assess the concordance …

Receptor Usage And Infection Biology Of Influenza D Virus, Tirth Uprety

Theses and Dissertations--Veterinary Science

Influenza D virus (IDV) utilizes bovines as a primary reservoir with periodical spillover to other hosts. We have previously demonstrated by the traditional hemagglutination assay coupled with sialoglycan microarray and functional assays that IDV can recognize and bind both 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac₂) and 9-O-acetylated N-glycolylneuraminic acid (Neu5Gc9Ac). Agricultural animals such as cattle can produce both Neu5,9Ac₂ and Neu5Gc9Ac, while humans are genetically unable to synthesize Neu5Gc9Ac. The bifunctional enzyme, glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) is a master regulator of de-novo sialic acid synthesis while 9-O-Acetylation of sialic acids is catalyzed by …

The Long-Term Effects Of Wildfire Severity On Oak-Pine Communities And Their Microclimates, Scott Glenn Culbert

Theses and Dissertations--Forestry and Natural Resources

In the eastern U.S., fire-dependent tree species have historically dominated upland forest communities, but are now experiencing widespread regeneration challenges as a result of 20^th century fire suppression policies, and are being replaced by mesophytic species. Wildfires that contain areas of high burn severity may provide an important means of mitigating these challenges and facilitating fire-dependent species regeneration and recruitment into larger size classes. One mechanism by which high-severity fire can accomplish this is by modifying understory microclimate characteristics to be more conducive to these species’ growth. A wildfire within the Daniel Boone National Forest, Kentucky, USA, provided the …

Economics Of Maple Syrup Production In Kentucky, Bobby Thapa

Theses and Dissertations--Forestry and Natural Resources

Maple syrup production is traditionally associated with New England regions in the United States, but there is growing interest in expanding it to other regions with suitable environmental conditions, including Kentucky. This study presents an in-depth analysis of the potential production and economic impacts of maple syrup in Kentucky using a multi-method approach. First, the study applies a stochastic production model to assess the effects of climatic and tree variables on maple syrup yield. The results reveal that several variables, including the number of maple trees, taps, temperatures, tapping season length, and time, significantly affect maple syrup yield. Second, input-output …

Effects Of Forest Reclamation And Landscape Features On Avian Occupancy, Species Richness, And Abundance In Appalachia, Rebecca N. Davenport

Theses and Dissertations--Forestry and Natural Resources

The Forestry Reclamation Approach (FRA) is a recently developed coal mining reclamation method that emphasizes best management practices in forestry, such as the planting of native trees and shrubs. Although the FRA is expected to benefit wildlife, no studies have empirically examined the effects of the FRA on avian species. My study aimed to identify which reclamation approaches and/or landscape features promote breeding songbirds, particularly mature forest avian guilds and species of conservation need. I conducted point count surveys in the Appalachian Mountains of eastern West Virginia and assessed differences in avian occupancy, species richness, and species abundance between four …

The Effect Of Land-Cover/Land-Use And Habitat Fragmentation On Spatial Patterns Of Lyme Disease In The Eastern United States, Maria Elizabeth Topmiller

Theses and Dissertations--Forestry and Natural Resources

Lyme disease has been of national concern for the past few decades. As our understanding of the role of landscape structure in epidemiology expands, it is essential to apply the principles of landscape ecology to the research of vector-borne and zoonotic disease. This study examined the strength of the relationship between land-cover class, degree of habitat fragmentation and county-level Lyme disease cases. Forest, agricultural, and urban land cover types were the categories of interest, while percent cover, edge density, and patch density were the landscape metric used to measure habitat amount and fragmentation. The general linear trends were modelled with …

Pond-Breeding Amphibian Responses To Wetland Creation And Reforestation On A Legacy Surface Mine In The Monongahela National Forest, Lauren Breanna Sherman

Theses and Dissertations--Forestry and Natural Resources

Surface mine reclamation has been an evolving practice since the Surface Mining Control and Reclamation Act was passed in 1977, holding mining companies accountable for returning ecological function to areas directly impacted by mining activities. One recent method of reclamation, the Forestry Reclamation Approach (FRA), aims to enhance reforestation and ecosystem function through the creation of wetlands, as opposed to traditional methods that often revert land to grasslands. However, wildlife response to FRA has rarely been investigated. The goal of this project was to analyze the effects of the four treatment types, FRA in two chronosequences, natural regeneration, and unmined …

Chemical Immobilization Of Helicopter-Captured Elk (Cervus Canadensis) And Survival Of Elk Calves In Southeastern Kentucky, Kathleen E. Williams

Theses and Dissertations--Forestry and Natural Resources

Safe and effective chemical immobilization is critical to minimize stress and risk of injury when capturing free-ranging, wild ungulates. Many traditionally favored high potency opioids have been phased out or become unavailable because of increased regulations, leading to the development of two pre-mixed combination drugs, butorphanol-azaperone-medetomidine (BAM) and nalbuphine-medetomidine-azaperone (NalMed-A). Both drugs have been used to chemically immobilize ungulates, but their efficacy has not been documented in elk captured and transported via helicopter. During 2020 – 2022, we chemically immobilized helicopter-captured female elk (Cervus canadensis) with a single IM-injection of BAM (n = 41) or NalMed-A (n = …

Nanopesticide Influence On Nitrogen Cycling In Soils, Jacob Richardson

Theses and Dissertations--Biosystems and Agricultural Engineering

Nanotechnology has several applications in the agricultural industry, as the small size of nanoparticles and high reactivity enables targeted delivery of pesticides and fertilizers to the intended crop. Copper-based nanopesticides such as Kocide, are proposed as a more efficient method for targeted pest control. Despite the potential benefits of nanopesticides, little is known regarding the transport and implications of nanopesticides under long-term inundation conditions often found in downstream wetlands. Specifically, the impact of nanopesticides on microbial nitrogen processes in wetland environments remains unknown. Therefore, this thesis explores the impact of nanopesticides, specifically Kocide, on microbial nitrogen cycles in agricultural and …